a study evaluating the efficacy and safety of divarasib and pembrolizumab versus pembrolizumab and pemetrexed and carboplatin or cisplatin in participants with previously untreated, kras g12c-mutated, advanced or metastatic non-squamous non-small cell lung cancer

Conditions: Non-Small Cell Lung Cancer; KRAS G12C Lung Cancer

Summary: the purpose of this study is to evaluate the efficacy and safety of divarasib and pembrolizumab compared with pembrolizumab and pemetrexed and carboplatin or cisplatin, for the first-line treatment of adult participants with kras g12c-mutated, advanced or metastatic non squamous non-small cell lung cancer (nsclc).


Eligibility criteria:
inclusion criteria: * eastern cooperative oncology group (ecog) performance status of 0 or 1 * histologically or cytologically confirmed diagnosis of advanced or metastatic non squamous nsclc that is not eligible for curative surgery and/or definitive chemoradiotherapy * measurable disease, as defined by recist v1.1 * no prior systemic treatment for advanced or metastatic nsclc * documentation of the presence of a kras g12c mutation * documentation of known pd-l1 expression status in tumor tissue * availability of a representative tumor specimen * adequate end-organ function * eligible to receive a platinum-based chemotherapy regimen exclusion criteria related to nsclc: * known concomitant second oncogenic driver with available targeted treatment * symptomatic, untreated, or actively progressing central nervous system (cns) metastases * spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for \>=2 weeks prior to randomization * history of leptomeningeal disease * uncontrolled tumor-related pain * uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once a month or more frequently) exclusion criteria related to current or prior treatments: * any anti-cancer systemic therapy, including hormonal therapy, within 21 days prior to randomization, or is expected to require any other form of antineoplastic therapy while in the study * radiation therapy including palliative rt to bone metastases within 2 weeks prior to randomization and rt to the lung \>30gy within 6 months prior to randomization * prior treatment with kras g12c inhibitors or pan-kras/ras inhibitors * treatment with systemic immunosuppressive or immunostimulatory medications, including cd137 agonists and immune checkpoint inhibitors * current treatment with medications that are well known to prolong the qt interval * treatment with therapeutic oral or iv antibiotics within 2 weeks prior to randomization * prior allogeneic stem cell or solid organ transplantation exclusion criteria related to general health: * history of malignancy other than nsclc within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year overall survival \[os\] rate \>90%), such as adequately treated carcinoma in situ of the cervix, non melanoma skin carcinoma, localized prostate cancer, ductal breast carcinoma in situ, or stage i uterine cancer * individuals with chronic diarrhea, short bowel syndrome or significant upper gastrointestinal surgery including gastric resection, a history of inflammatory bowel disease (e.g., crohn's disease or ulcerative colitis) or any active bowel inflammation (including diverticulitis), malabsorption syndrome, conditions that would interfere with enteral absorption * history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on the screening chest computed tomography scan * significant cardiovascular disease within 3 months prior to screening

Keywords: advanced non-small cell lung cancer kras g12 lung cancer advanced lung cancer metastatic lung cancer divarasib kras g12c inhibitor kras g12c positive kras mutation kras g12c mutation lung cancer mutation